Upregulation of TRPC1 in the development of cardiac hypertrophy
Upregulation of TRPC1 in the development of cardiac hypertrophy
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DOI：
10.1016/j.yjmcc.2006.10.020
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发表时间：
2007-03-01
影响因子：
5
通讯作者：
Ito, Hiroshi
中科院分区：
文献类型：
--
作者：
Ohba, Takayoshi;Watanabe, Hiroyuki;Ito, Hiroshi
钙离子内流在心肌肥厚反应中的重要性已有充分文献记载，但实际的钙离子内流通道仍不明确。瞬时受体电位（TRP）蛋白被认为可形成同聚体或异聚体钙离子内流通道，参与多种细胞的增殖和分化。本研究的目的是探讨TRP通道在心肌肥厚发展中的潜在作用。利用腹主动脉缩窄（AAB）大鼠的心脏评估了几种TRP通道亚基的mRNA和蛋白质表达。尽管TRPC1、TRPC3、TRPC5和TRPC6组成性表达，但与假手术大鼠相比，AAB大鼠心脏中只有TRPC1的表达显著增加。利用新生大鼠心肌细胞原代培养，我们检测到在内皮素 - I（ET - 1）处理后，TRPC1、脑钠肽（BNP）和心房钠肽（ANF）的表达增加，以及钙库操纵性钙离子内流（SOCE）和细胞表面积增加。通过小干扰RNA（siRNA）沉默TRPC1基因可减弱SOCE，并阻止ET - 1、血管紧张素 - II（AT II）和苯肾上腺素（PE）诱导的心肌肥厚。在HEK 293T细胞中，TRPC1的过表达增强了SOCE，导致活化T细胞核因子（NFAT）启动子活性增加，而与显性负性形式的TRPC1共转染则抑制了它。总之，TRPC1在钙离子内流中起作用，其上调参与心肌肥厚的发展；此外，它在调控心肌肥厚的信号通路中起重要作用。这些发现确立了TRPC1是心肌肥厚的一个功能重要的调节因子。（c）2006爱思唯尔公司。保留所有权利。
The importance of Ca2+ entry in the cardiac hypertrophic response is well documented, but the actual Ca2+ entry channels remain unknown. Transient receptor potential (TRP) proteins are thought to form either homo- or heteromeric Ca2+ entry channels that are involved in the proliferation and differentiation of various cells. The purpose of this study was to explore the potential involvement of TRP channels in the development of cardiac hypertrophy. The mRNA and protein expression of several TRP channel subunits were evaluated using hearts from abdominal aortic-banded (AAB) rats. Although TRI's C1, C3, C5, and C6 were constitutively expressed, only TRPC1 expression was significantly increased in the hearts of AAB rats compared to sham-operated rats. Using primary cultures of neonatal rat cardiomyocytes, we detected increases in the expression of TRPC1, brain natriuretic peptide (BNP), and atrial natriuretic factor (ANF), as well as increases in store-operated Ca2+ entry (SOCE) and cell surface area, following endothelin-I (ET-1) treatment. Silencing of the TPPC1 gene via small interfering RNA (siRNA) attenuated SOCE and prevented ET-1-, angiotensin-II (AT II)-, and phenylephrine (PE)-induced cardiac hypertrophy. In HEK 293T cells, overexpression of TRPC1 augmented SOCE, leading to an increase in nuclear factor of activated T cells (NFAT) promoter activity, while co-transfection with dominant-negative forms of TRPC1 suppressed it. In conclusion, TRPC1 functions in Ca2+ influx, and its upregulation is involved in the development of cardiac hypertrophy; moreover, it plays an important role in the regulation of the signaling pathways that govern cardiac hypertrophy. These findings establish TRPC1 as a functionally important regulator of cardiac hypertrophy. (c) 2006 Elsevier Inc. All rights reserved.